Resistance to anticancer drugs in NIH3T3 cells transfected with c-myc and/or c-H-ras genes.

NIH3T3 cells transfected with c-H-ras and/or c-myc genes were examined for differences in drug sensitivity. The five transfectants used were N8, NIH3T3-nm-1, pT22-3-nm-2, pP1-4 and pT22-3. They were transfected with pKOneo alone, pKOneo and c-myc, pKOneo and c-myc plus activated c-H-ras, normal c-H-ras and activated c-H-ras genes, respectively. The IC50s of cisplatin, 4-hydroperoxycyclophosphamide, adriamycin, melphalan, and CPT-11 were significantly higher for NIH3T3-nm-1 abd pT22-3-nm-2 than for the parental NIH3T3 and N8 cells. Transfection with normal and activated C-H-ras oncogenes only led to increases in the IC50s of alkylating agents. There was no significant difference between the IC50s of N8 and those of NIH3T3 parental cells to any of these anticancer agents. These results strongly suggest that the expression of the c-myc gene plays a role in the acquisition of drug resistance. The c-myc gene may therefore provide us with an important clue in determining the mechanism of drug resistance.

[1]  W. McGuire,et al.  Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. , 1987, Science.

[2]  M. Barbacid,et al.  T24 human bladder carcinoma oncogene is an activated form of the normal human homologue of BALB- and Harvey-MSV transforming genes , 1982, Nature.

[3]  M. Viola,et al.  ras Oncogene p21 expression is increased in premalignant lesions and high grade bladder carcinoma , 1985, The Journal of experimental medicine.

[4]  M. Erisman,et al.  Structure and expression of the oncogene c-myc in fresh tumor material from patients with hematopoietic malignancies , 1984, Molecular and cellular biology.

[5]  P. Chomczyński,et al.  Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. , 1987, Analytical biochemistry.

[6]  A. Viel,et al.  Sensitivity Pattern of Normal and Ha-Ras Transformed Nih3T3 Fibroblasts to Antineoplastic Drugs , 1989, Tumori.

[7]  T. Mosmann.  Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. , 1983, Journal of immunological methods.

[8]  H. Sather,et al.  Association of multiple copies of the N-myc oncogene with rapid progression of neuroblastomas. , 1985, The New England journal of medicine.

[9]  J. Minna,et al.  Characterization of variant subclasses of cell lines derived from small cell lung cancer having distinctive biochemical, morphological, and growth properties. , 1985, Cancer research.

[10]  E. Southern.  Detection of specific sequences among DNA fragments separated by gel electrophoresis. , 1975, Journal of molecular biology.

[11]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[12]  M. Muramatsu,et al.  Structure and expression of a human class pi glutathione S-transferase messenger RNA. , 1987, Cancer research.

[13]  R T Schimke,et al.  Gene amplification, drug resistance, and cancer. , 1984, Cancer research.

[14]  R. Makuch,et al.  myc family oncogene amplification in tumor cell lines established from small cell lung cancer patients and its relationship to clinical status and course. , 1987, The Journal of clinical investigation.

[15]  I. Pastan,et al.  Isolation of human mdr DNA sequences amplified in multidrug-resistant KB carcinoma cells. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[16]  M. Sklar.  Increased resistance to cis-diamminedichloroplatinum(II) in NIH 3T3 cells transformed by ras oncogenes. , 1988, Cancer research.

[17]  J. Minna,et al.  Amplification and expression of the c-myc oncogene in human lung cancer cell lines , 1983, Nature.

[18]  M. Wigler,et al.  Human-tumor-derived cell lines contain common and different transforming genes , 1981, Cell.

[19]  J. Battey,et al.  L-myc, a new myc-related gene amplified and expressed in human small cell lung cancer , 1985, Nature.

[20]  V. Ling,et al.  Detection of P-glycoprotein in ovarian cancer: a molecular marker associated with multidrug resistance. , 1985, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  J. Yokota,et al.  LEVELS OF GLUTATHIONES TRANSFERASE π mRNA IN HUMAN LUNG CANCER CELL LINES CORRELATE WITH THE RESISTANCE TO CISPLATIN AND CARBOPLATIN , 1988, Japanese journal of cancer research : Gann.

[22]  S. Thorgeirsson,et al.  Transformation of rat liver epithelial cells with v-H-ras or v-raf causes expression of MDR-1, glutathione-S-transferase-P and increased resistance to cytotoxic chemicals. , 1988, Carcinogenesis.

[23]  M. Wigler,et al.  Isolation and preliminary characterization of a human transforming gene from T24 bladder carcinoma cells , 1982, Nature.

[24]  M. Wigler,et al.  New human transforming genes detected by a tumorigenicity assay , 1984, Molecular and cellular biology.

[25]  J. Isbister,et al.  DETECTION OF A MULTIDRUG RESISTANT PHENOTYPE IN ACUTE NON-LYMPHOBLASTIC LEUKAEMIA , 1987, The Lancet.

[26]  V. Ling,et al.  P-glycoprotein expression in multidrug-resistant human ovarian carcinoma cell lines. , 1989, Cancer research.

[27]  H. Varmus,et al.  Molecular cloning and characterization of avian sarcoma virus circular DNA molecules , 1980, Journal of virology.

[28]  A. Tulpule,et al.  Similar biochemical changes associated with multidrug resistance in human breast cancer cells and carcinogen-induced resistance to xenobiotics in rats. , 1986, Proceedings of the National Academy of Sciences of the United States of America.